MEsenchymal StEm cells for Multiple Sclerosis (MESEMS): a multi-center, randomized, double blind, cross-over phase 2 clinical trial with autologous mesenchymal stem cells (MSC)
ECTRIMS Online Library. Uccelli A. Sep 13, 2019; 278579; P1378
Prof. Antonio Uccelli
Prof. Antonio Uccelli
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Abstract

Abstract: P1378

Type: Poster Sessions

Abstract Category: Therapy - Neuroprotection and Repair

A. Uccelli1,2, A. Laroni1,2, L. Brundin3, M. Clanet4, O. Fernandez5,6, S. Massood Nabavi7,8, P.A. Muraro9, R.S. Oliveri10, E.W. Radue11, J.T. Sellner12, P. Soelberg Sorensen13, M.P. Sormani2,14, J.T. Wuerfel11,15, M.A. Battaglia16,17, M.S. Freedman18, MESEMS study group

1Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health and Center of Excellence for Biomedical Research (CEBR), University of Genova, 2IRCCS Ospedale Policlinico San Martino, Genova, Italy, 3Karolinska Institutet, R3:04 Karolinska University Hospital, Stockholm, Sweden, 4CHU Toulouse, Université Paul Sabatier, INSERM UMR 1043, Toulouse, France, 5Instituto de Investigación Biomédica de Málaga (IBIMA), 6Regional University Hospital of Malaga, Malaga, Spain, 7Royan Institute for Stem Cell Biology and Technology, Royan, 8ACCR, Iran and Regenerative Biomedicine Center, MS, Neurology Clinic and Research Unit, Tehran, Islamic Republic of Iran, 9Department of Brain Sciences, Faculty of Medicine, Imperial College London, London, United Kingdom, 10Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark, 11Medical Image Analysis Centre Basel, Basel, Switzerland, 12Christian Doppler Medical Center, Paracelsus Medical University, Salzburg, Austria, 13University of Copenhagen, Rigshospitalet Danish MS Center, Copenhagen, Denmark, 14University of Genova, Genova, Italy, 15Department of Biomedical Engineering, University Basel, Basel, Switzerland, 16Italian Multiple Sclerosis Foundation, Genova, 17Department of Life Sciences, University of Siena, Siena, Italy, 18Department of Medicine (Neurology), University of Ottawa and The Ottawa Hospital Research Institute, Ottawa, ON, Canada

Introduction: Bone marrow-derived Mesenchymal stromal/stem cells (MSC) are multipotent cells with anti-inflammatory and neuroprotective potential, demonstrated in pre-clinical EAE studies; administered MSC ameliorated the disease course, decreased the immune infiltrate and stemmed neuronal loss. Phase 1 human MS trials with autologous MSC have consistently demonstrated safety, paving the way for a proof of concept phase II trial examining safety and efficacy measures.
Methods: MESEMS is an international, multi-center phase II double-blind, randomized, cross-over, placebo-controlled trial lasting 56 weeks. Enrolled patients included active relapsing remitting (RR), secondary progressive (SP) or primary progressive (PP) patients who were randomized to receive intravenously (iv) either autologous MSC at a dose of 1-2 x 10.6/Kg or sham MSC infusion (placebo). At 24 weeks, treatments were switched. The primary endpoints are safety, as measured by the number and severity of adverse events (AE) and efficacy in terms of reduction, as compared to placebo, in the total number of contrast-enhancing lesions (GEL) on MRI over 24 weeks. Secondary efficacy outcomes included evaluation of treatment on combined unique MRI activity at 24 and 48 weeks, and on clinical and neuropsychological measures. To overcome the financial and practical constraints of an academic-driven clinical trial employing a cellular product, the MESEMS trial was unique in that it was conducted as a merger of partially independently funded clinical trials, all following the same protocol and collecting data blindly using a central unbiased CRO.
Results: 15 centers from 9 countries participated in MESEMS, which screened 163 patients and randomized 144 patients. Baseline clinical data are available for 140 patients, with active RR MS (N=92), SP MS (N= 31) or PP MS (N=17): F/M ratio 1.55; median baseline EDSS 4.0, mean number of relapses in the two previous years 1.60 median EDSS worsening in the year before randomization was 0.5. 139 patients received both treatments, 144 patients received only the first treatment and 5 dropped out before receiving the second.
Conclusions: The clinical trial is ongoing with the last patient, last visit expected in July, 2019. Following study completion the data will be unblinded and we will present the primary safety and efficacy measures of MESEMS.
Disclosure:
Antonio Uccelli has received personal compensation from Novartis, TEVA, Biogen, Merck, Roche and Genzyme for public speaking and advisory boards
Alice Laroni has received personal compensation from Novartis, Sanofi Genzyme, Biogen, Merck, Roche, and TEVA for public speaking and advisory boards.
Lou Brundin has recieved travel grants and lecturing fees from Sanofi/ Genzyme, Biogen and Amirall and has participated in advisory boards for Genzyme, Sanofi, Biogen, Amirall and Merck. Brundin has grants from Swedish medical research foundation, the Brain foundation, Stockholm Council and Karolinska Instituet.
Michel Clanet: no conflict of interest to declare
Oscar Fernandez, has received honoraria from Actelion, Allergan, Almirall, Bayer Schering, Biogen, Merck Serono, Novartis, Roche, and Teva
Seyed Massoud Nabavi has received honoraria from, Biogen, Bayer, Genzyme,, Merck Serono, Novartis, Sanofi, Abidi co., Zist daru co., Actoverco co. as PI of trials grants or speaker bureau.
Paolo Muraro reports no conflict of interest. He discloses travel support and speaker honoraria from Bayer HealthCare, Bayer Pharma, Biogen Idec, Merck-Serono and Sanofi Aventis.
Roberto S. Oliveri is currently a full-time employee at Genmab.
Ernst Radue: no conflict of interest to declare
Johann Sellner received support for attending scientific conferences, advisory boards, lectures and consultancy within the last 12 months from Bayer, Biogen, MedDay, Merck, Novartis, Roche, Sanofi-Genzyme.
Per Soelberg Sorensen has received personal compensation for serving on scientific advisory boards, steering committees, independent data monitoring committees or have received speaker honoraria for Merck, Novartis, TEVA, GlaxoSmithKline, MedDay Pharmaceuticals, SanofiAventis/Genzyme, and Celgene.
Maria Pia Sormani received compensation for serving on the Scientific Advisory Boards of Teva, Genzyme, Novartis, Roche and Vertex; funding for travel or speaker honoraria from Merck Serono, Teva, Genzyme, Novartis, Biogen and Roche; consultancy from Merck Serono, Biogen, Teva, Genzyme, Roche, GeNeuro, MedDay and Novartis; Speakers´ Bureaus from Teva, Merck Serono, Biogen, Novartis and Genzyme.
Jens Thomas Wuerfel is CEO of MIAC AG, Switzerland. He served on advisory boards for Actelion, Biogen, Genzyme-Sanofi, Novartis and Roche. He received funds from EU (Horizon2020), the German Research Foundation (DFG), the German Ministeries of Science and Economy (BMBF, BMWi) unrelated to this study.
Mario Alberto Battaglia has nothing to disclose.
Mark S. Freedman has received honoraria from Actelion, Biogen, Bayer, Celgene, Chugai, EMD Inc., Genzyme, Hoffman La Roche, Merck Serono, Novartis, Pendopharm, and Sanofi; Grants from Genzyme and is on the Genzyme speakers' bureau.

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